RNA Delivery May Bring Stronger Vaccines

With science and technology advancing every day, new discoveries are also being made in the medicine world. Medical Scientists are working on new drugs that are more powerful and act faster in treating the same diseases. Diseases that were once incurable can now be prevented with a vaccine, and in case caught can be treated with a few tablets or injections. 

One of these remarkable discoveries that scientists believe holds great potential are vaccines made from RNA. These drugs can be used to treat cancer and also for the prevention of many infectious diseases. Because of their promising results, biotech companies are conducting more research on such vaccines, and a few of them have even gone through clinical trials.

However, they are facing some issues. One of these issues is that they must make sure the RNA gets into the right immune cells, and once it gets there, it must also produce the right amount of encoded protein. Another challenge is that the vaccine must be strong enough to stimulate a reaction big enough that wipes out all the relevant microorganisms causing the disease. 

Chemical Engineers from MIT have developed a series of lipid nano-particles that deliver such vaccines. In a study performed on mice, their newly developed RNA vaccine successfully managed to inhibit the growth of tumors. This study was performed on two different mice with melanoma, and in both cases, the growth of the tumor was slowed down, and the rate of survival increased.

An associate professor at MIT, Daniel Anderson, spoke about their study, saying that one of the discoveries of their study is that we can make RNA delivery lipids that can even be used to activate the immune system.

Traditional vaccines are made up of infectious microbes in weakened forms. The scientists then came up with the idea of making vaccines using DNA that can encode microbial proteins. However, the results of this study were not as promising as that of RNA.. 

Anderson, with his team, developed many lipid nanoparticles that protect and deliver RNA to its desired destination. Their aim is to develop carriers.

Do you think RNA will be successful in treating patients?

The Blood Barrier in Alzheimer’s

A blood-brain barrier is a rigid barrier which prevents damaging molecules in the blood from the brain. Beta-amyloid plaques, which are clusters of proteins found in the brains of Alzheimer’s patients, can damage neurons and compromise brain functions.

The detriments caused by beta-amyloid plaques in the brain can further damage the Alzheimer’s neurons by allowing the blood-clotting protein, thrombin, to enter the brain. Once the barrier is impaired, chemicals are secreted into the brain, which impedes brain functions and adversely affect neuron health.

Barrier Breakdown

Cells in the blood vessels that form a blood-brain barrier comprise specialized proteins that assist them in making tight junctions which act as tough seals in between cells.

Beta-amyloid plaques have a damaging effect on the brain known as the Cerebral Amyloid Angiopathy (CAA). Researchers believe that this effect allows detrimental substances to enter the brain more easily.

The researchers in the Massachusetts Institute of Technology (MIT) grew beta-amyloid plaques in a microfluidic channel, as well as the brain endothelium cells. The two projects were separated by an empty channel during the development of each tissue.

After ten days, collagen was introduced in the empty channel, which acted as a diffusion medium for the molecules to diffuse from one channel to the other. It was discovered that within three to six days, the beta-amyloid plaques had started adhering to the endothelium tissue, causing it to become leakier. The endothelium cells showed a reduction in the proteins that form tight barriers between cells and increased secretion of a particular enzyme that disrupted the layered matrix, which normally surrounds the blood vessels.

The breakdown of the blood-brain barrier resulted in an eased flow of thrombin from blood in the leaky blood vessels to the brain, where it can have adverse effects on neurons and harm neuron health.

Preventing the leakage

Next up, the researchers determined to test two types of antidotes that are FDA (Food and Drug Administration) approved to treat all kinds of conditions. These drugs were previously proven to strengthen the weak blood-brain barriers in relatively simple endothelium tissue models. The researchers discovered that the first drug, etodolac, worked very efficiently and effectively in solidifying the blood-brain barrier, while the other drug, beclomethasone, did little to stop and treat the leakages in the endothelium tissue experiments.

The backstory is that the leakages treated using etodolac caused the blood-brain barrier to become tighter and more rigid, and survival rates of neurons boosted. The MIT and Massachusetts General Hospital (MGH) have now teamed up with a drug discovery association to find other drugs that may be successful in revitalizing the blood-brain barrier in Alzheimer’s patients.  

Conclusion

So far, treatments for Alzheimer’s have proven unsuccessful. Therefore, the researchers in MIT intend to use this method to identify more drugs that originate from single-cell screens, in order to pass them through a newly tested, complex process which could become a potential form of reliable treatment for Alzheimer’s patients.

MIT Scientists Research The Fluid That Feeds Tumor Cells

Every cell requires a specific environment to grow and to nourish so does cancer cells. Before testing cancer cell in any living organism, they tested in labs with the proper environment, but from last few years, researchers have noticed that the fluid in which the cancer cells grow in the body is entirely different from the fluid which is provided in labs, and this massive change can alter the effects.

The MIT biologists have researched about it and found that the interstitial fluid which is provided to the cancer cells in labs have an entirely different composition than the natural the fluid they get.

Matthew Vander Heiden, an associate professor of biology at MIT suggested that to grow the cancer cell in the medium similar to the original medium would be more helpful in observing the effect of experimental drugs on the cells.

As the cancer cells metabolize differently in the body as any other cells and use the alternative strategy to grow and divide. And in recent years, many medicines are under development to hinder this type of metabolism. The scientist used to have the carbon-based medium for the cancer cells. However, MIT biologist found that they act differently in the lab dish as well as the mouse they have used for the experiment.

Vander Heiden said that “it was a wakeup call for us that to know how to find the dependencies of cancer, we have to get the environment right.” After this keen observation, the scientist started to investigate the composition of the fluid which helps the cells to grow. Because without the knowledge of the environment which provides help, how can we stop cancer from growing?

It was definite that the fluid is not blood, because the tumors usually do not have any connection with the blood supply. To find out, the biologist used the pancreatic tumor, because it is known as a nutrient deprived source. After extracting the interstitial fluid from the mice. They used a mass spectrometric procedure to find out the composition of the fluid. The results showed that the fluid was depleted of many types of amino acids especially the ones which promotes the immunity and cell functioning and those are arginine, tryptophan, and cystine whereas some amino acids like glycine and glutamate which are known to be produced by the cancer cells were still present.

During this investigation, they also observed that the location of the cancer cells is also a factor of having different fluid environment. Because when the investigation moved further and cancer cells from lungs were tested, they had a different environment than the pancreatic cancer cells. And in some cases, there was a slight difference in the fluid according to the genetic makeup. But genes did not have a significant impact on the type of environment.

The scientist has a theory that the surrounding supportive cells are recruited by the cancer cells which makes the environment of that specific cancer type. Now the MIT labs are working making the closest mimic of the fluid, to get the best results of experimental drugs.

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